scholarly journals Low dose Cold Atmospheric Plasma induces membrane oxidation, stimulates endocytosis and enhances uptake of nanomaterials in Glioblastoma multiforme cells

2019 ◽  
Author(s):  
Zhonglei He ◽  
Kangze Liu ◽  
Laurence Scally ◽  
Eline Manaloto ◽  
Sebnem Gunes ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Membrane Damage ◽  
Cellular Membrane ◽  
Atmospheric Plasma ◽  
Ros Generation ◽  
Main Role ◽  
Cancer Therapies ◽  
Membrane Repair ◽  
Cold Atmospheric Plasma ◽  
Therapy And Diagnosis

AbstractCold atmospheric plasma (CAP) has demonstrated synergistic cytotoxic effects with nanoparticles, especially promoting the uptake and accumulation of nanoparticles inside cells. However, the mechanisms driving the effects need to be explored. In this study, we investigate the enhanced uptake of theranostic nanomaterials by CAP. Numerical modelling of the uptake of gold nanoparticle into U373MG Glioblastoma multiforme (GBM) cells predicts that CAP may introduce a new uptake route. We demonstrate that cell membrane repair pathways play the main role in this stimulated new uptake route, following non-toxic doses of dielectric barrier discharge CAP (30 s, 75 kV). CAP treatment induces cellular membrane damage, mainly via lipid peroxidation as a result of reactive oxygen species (ROS) generation. Membranes rich in peroxidated lipids are then trafficked into cells via membrane repairing endocytosis. We confirm that the enhanced uptake of nanomaterials is clathrin-dependent using chemical inhibitors and silencing of gene expression. Therefore, CAP-stimulated membrane repair increases endocytosis and accelerates the uptake of gold nanoparticles into U373MG cells after CAP treatment. Our data demonstrate the utility of CAP to model membrane oxidative damage in cells and characterise a previously unreported mechanism of membrane repair to trigger nanomaterial uptake which will be useful for developing more efficient deliveries of nanoparticles and pharmaceuticals into cancer cells for tumour therapy and diagnosis. This mechanism of RONS-induced endocytosis will also be of relevance to other cancer therapies that induce an increase in extracellular RONS.

INTRACRANIAL TARGETING OF GLIOBLASTOMA MULTIFORME WITH COLD ATMOSPHERIC PLASMA

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Hayk Simonyan ◽  
Zhitong Chen ◽  
Jonathan Sherman ◽  
Xiaoqian Cheng ◽  
Michael Keidar ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Atmospheric Plasma ◽  
Cold Atmospheric Plasma

scholarly journals Cold Atmospheric Plasma induces accumulation of lysosomes and caspase-independent cell death in U373MG glioblastoma multiforme cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gillian E. Conway ◽  
Zhonglei He ◽  
Ana Lacramioara Hutanu ◽  
George Paul Cribaro ◽  
Eline Manaloto ◽  
...  
Keyword(s):  
Cell Death ◽  
Glioblastoma Multiforme ◽  
Plasma Treatment ◽  
Acridine Orange ◽  
Molecular Mechanisms ◽  
Confocal Imaging ◽  
Atmospheric Plasma ◽  
Cold Atmospheric Plasma ◽  
Rapid Accumulation ◽  
Lysosomal Accumulation

Abstract Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma treated cells that stained positive with acridine orange. Western immunoblotting confirmed that autophagy is not activated following plasma treatment. Acridine orange intensity correlates closely with the lysosomal marker Lyso TrackerTM Deep Red. Further investigation using isosurface visualisation of confocal imaging confirmed that lysosomal accumulation occurs in plasma treated cells. The accumulation of lysosomes was associated with concomitant cell death following plasma treatment. In conclusion, we observed rapid accumulation of acidic vesicles and cell death following CAP treatment in GBM cells. We found no evidence that either apoptosis or autophagy, however, determined that a rapid accumulation of late stage endosomes/lysosomes precedes membrane permeabilisation, mitochondrial membrane depolarisation and caspase independent cell death.

Anti-Cancer Therapies of 21st Century: Novel Approach to Treat Human Cancers Using Cold Atmospheric Plasma

2014 ◽  
Vol 11 (12) ◽  
pp. 1128-1137 ◽  
Author(s):  
Edward A. Ratovitski ◽  
Xiaoqian Cheng ◽  
Dayun Yan ◽  
Jonathan H. Sherman ◽  
Jerome Canady ◽  
...  
Keyword(s):  
21St Century ◽  
Atmospheric Plasma ◽  
Cancer Therapies ◽  
Cold Atmospheric Plasma ◽  
Human Cancers ◽  
Novel Approach ◽  
Anti Cancer

scholarly journals Pyruvate Plays a Main Role in the Antitumoral Selectivity of Cold Atmospheric Plasma in Osteosarcoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Juan Tornin ◽  
Miguel Mateu-Sanz ◽  
Aida Rodríguez ◽  
Cédric Labay ◽  
Rene Rodríguez ◽  
...  
Keyword(s):  
Atmospheric Plasma ◽  
Main Role ◽  
Cold Atmospheric Plasma

scholarly journals Acidified Nitrite Contributes to the Antitumor Effect of Cold Atmospheric Plasma on Melanoma Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3757
Author(s):  
Tom Zimmermann ◽  
Lisa A Gebhardt ◽  
Lucas Kreiss ◽  
Christin Schneider ◽  
Stephanie Arndt ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Membrane Damage ◽  
Melanoma Cells ◽  
Atmospheric Plasma ◽  
Active Components ◽  
Antitumor Effects ◽  
Cold Atmospheric Plasma ◽  
Viability Analysis ◽  
Cellular Effects ◽  
The Impact

Cold atmospheric plasma (CAP) is partially ionized gas near room temperature with previously reported antitumor effects. Despite extensive research and growing interest in this technology, active components and molecular mechanisms of CAP are not fully understood to date. We used Raman spectroscopy and colorimetric assays to determine elevated nitrite and nitrate levels after treatment with a MiniFlatPlaster CAP device. Previously, we demonstrated CAP-induced acidification. Cellular effects of nitrite and strong extracellular acidification were assessed using live-cell imaging of intracellular Ca2+ levels, cell viability analysis as well as quantification of p21 and DNA damage. We further characterized these observations by analyzing established molecular effects of CAP treatment. A synergistic effect of nitrite and acidification was found, leading to strong cytotoxicity in melanoma cells. Interestingly, protein nitration and membrane damage were absent after treatment with acidified nitrite, thereby challenging their contribution to CAP-induced cytotoxicity. Further, phosphorylation of ERK1/2 was increased after treatment with both acidified nitrite and indirect CAP. This study characterizes the impact of acidified nitrite on melanoma cells and supports the importance of RNS during CAP treatment. Further, it defines and evaluates important molecular mechanisms that are involved in the cancer cell response to CAP.

scholarly journals Cold Atmospheric Plasma induces silver nanoparticle uptake, oxidative dissolution and enhanced cytotoxicity in Glioblastoma multiforme cells

2020 ◽  
Author(s):  
Eline Manaloto ◽  
Aoife Gowen ◽  
Anna Lesniak ◽  
Zhonglei He ◽  
Alan Casey ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Cancer Cells ◽  
Barrier Discharge ◽  
Atmospheric Plasma ◽  
Imaging Method ◽  
Discharge System ◽  
Cold Atmospheric Plasma ◽  
Surface Charge Distribution ◽  
Synergistic Cytotoxicity

AbstractSilver nanoparticles (AgNP) emerged as a promising reagent for cancer therapy with oxidative stress implicated in the toxicity. Meanwhile, studies reported cold atmospheric plasma (CAP) generation of reactive oxygen and nitrogen species has selectivity towards cancer cells. Gold nanoparticles display synergistic cytotoxicity when combined with CAP against cancer cells but there is a paucity of information using AgNP, prompting to investigate the combined effects of CAP using dielectric barrier discharge system (voltage of 75 kV, current is 62.5mA, duty cycle of 7.5kVA and input frequency of 50-60Hz) and 10nm PVA-coated AgNP using U373MG Glioblastoma Multiforme cells. Cytotoxicity in U373MG cells was >100-fold greater when treated with both CAP and PVA-AgNP compared with either therapy alone (IC50 of 4.30 μg/mL with PVA-AgNP alone compared with 0.07 μg/mL after 25s CAP and 0.01 μg/mL 40s CAP). Combined cytotoxicity was ROS-dependent and was prevented using N-Acetyl Cysteine. A novel darkfield spectral imaging method investigated and quantified AgNP uptake in cells determining significantly enhanced uptake, aggregation and subcellular accumulation following CAP treatment, which was confirmed and quantified using atomic absorption spectroscopy. The results indicate that CAP decreases nanoparticle size, decreases surface charge distribution of AgNP and induces uptake, aggregation and enhanced cytotoxicity in vitro.

scholarly journals Cold atmospheric plasma induces GSDME-dependent pyroptotic signaling pathway via ROS generation in tumor cells

2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Xiaorui Yang ◽  
Guodong Chen ◽  
Kwan Ngok Yu ◽  
Miaomiao Yang ◽  
Shengjie Peng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Tumor Cells ◽  
Atmospheric Plasma ◽  
Ros Generation ◽  
Cold Atmospheric Plasma
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